The hypothalamic neuropeptide somatostatin (SRIF) acts in a multitude of organs and target tissues throughout the body, fundamentally exercising a inhibiting effect, whether over the secretion and regulation of other hormones or other diverse biological processes (Moller et al., 2003).
This action, which is generally inhibiting, but on some occasions stimulating, (Casta{umlaut over (n)}o et al., 1996) is exercised through a family of seven transmembrane domain (7TMD) type receptors coupled to G-proteins (GPCR), called somatostatin or ssts receptors. All ssts share a common structure consisting of an extracellular amino-terminal end connected to seven hydrophobic domains inserted into the membrane, which are in turn joined together through eight hydrophilic domains, and they end in an intracellular carboxyl-terminal end, which is important for the modulation of second messenger routes.
Up to the present, there are five different subtypes of ssts in mammals, from sst1 to sst5, and there are also two isoforms from subtype 2 (sst2A and sst2B) in mice and rats produced through alternative adjustment of the precursor messenger RNA which code two different proteins in the intracellular carboxyl-terminal region which present different properties with regard to the modulation of intracellular signaling routes. In fish, however, other isoforms from each receptor subtype have been discovered due to gene duplication phenomenon in place of other differential adjustment phenomenon of the messenger RNA that codes each of the isoforms.
The GPCRs, including the ssts, are involved in numerous medically relevant cellular processes, measured by signal transduction routes through G proteins. More specifically, one of these ssts subtypes, the human sst5 (WO 0177172, WO 0155319, WO 0136446, EP 1369698, WO 03104816) has been linked to a multitude of diverse pathologies in mammals, such as hematological and cardiovascular diseases, central and peripheral nervous system disorders, cancer, inflammatory processes, hepatic diseases, gastrointestinal and genito-urinary diseases (WO 03104816).
The human somatostatin receptor type 5, sst5, is recorded in public data bases with access numbers, including but not limited to GI39756975, GI21954086, GI13937340, which contain sequences pertaining to the DNA copy of the coding sequence, as well as genomic sequences that contain the complete gene structure of said receptor, and in addition to the coding sequence, the promoter region contains intronic sequences and uncoded 5′ and 3′ regions. As of the present, no alternative processing of human sst5 messenger RNA has been described which brings about any different alternative isoforms other than that which is recorded in the databases and thoroughly described in the bibliography.
The sequence corresponding to messenger RNA which contains the coding sequence of the porcine sst5 receptor, as well as the uncoded 5′ (GI58223147) and 3′ regions, have recently been cloned (Duran et al., 2005; awaiting publication). During the cloning process of the porcine sst5 through the RACE PCR technique, partial, and then total sequences of messenger RNA variants had been obtained through alternative adjustment, which coded two new receptor isoforms, as was the case of rat sst2, but in this case, they coded six and three transmembrane domains called porcine sst5B and sst5C isoforms (p-sst5B and p-sst5C), respectively.
There is data on truncated GPCRs produced by alternative adjustment of messenger RNA, which code proteins that form structures of less than seven transmembrane domains, as has been previously described for GHRH receptors (Rekasi et al., 2000), GnRH (Pawson et al., 2005), prostaglandin (Ishii et al., 2001), etc., some of which are functional with potential relevance in tumor processes. According to the results obtained for porcine sst5, cloning of potential human homologues of the porcine sst5B and sst5C isoforms was initiated through RACE PCR, in order to subsequently evaluate their presence and significance in endocrine tumors through the PCR technique.